Process and apparatus for producing an aerosol from a pulverulent substance

ABSTRACT

A process for producing an aerosol from a pulverulent substance, particularly for inhalation. In a turbulent agitating or whirling chamber, firstly a vacuum is produced, then gas is allowed to flow into the agitating chamber in such a way that the pulverulent substance contained therein is whirled up and an aerosol is produced, and immediately thereafter aerosol is discharged from the aerosol-containing agitating chamber.

BACKGROUND OF THE INVENTION

The invention relates to a process and an apparatus for producing anaerosol from a pulverulent substance, particularly a medicinalsubstance.

For the treatment of diseases of the respiratory tracts, medicinalsubstances are preferably applied by inhalation, because as a result theactive substance is deposited in relatively high concentration on therespiratory tracts, whereas effects due to the distribution of themedicinal substance throughout the body, so-called systemic effects,remain relatively limited. In addition, the inhalation of a medicinalsubstance is also suitable for systemic therapy.

The production of a suitable aerosol with effectively inhalable, i.e.relatively small, particles in part leads to considerable difficulties,particularly when based on a pulverulent substance. Therefore numerousprocesses and apparatuses have been developed which in different waysattempt to produce such a readily inhalable aerosol.

Despite the numerous possibilities in connection with inhalators the useof propellants, particularly those prejudicial to the environment, mustbe avoided. DE-A1-40 27 390 discloses a propellant-free inhalator, inwhich the medicinal substance is received in powder form in a storagecontainer. By means of a dosing device the substance dose is removedprior to the fitting of a mouthpiece, and from there the patient inhaleswith the aid of active breathing in, the substance being entrained bythe air flow formed as a result of breathing in. In order to obtaininhalable particles of the pulverulent substance, there is an airchamber for distributing the substance in the air flow being formed. Theparticle size in the case of this inhalator is dependent to asignificant extent on the intensity and nature of breathing in, so thatadequately small particles of the dosed substance cannot be guaranteedin all cases. For use in the known inhalator the medicinal substance,optionally accompanied by the admixing of adjuvants, is compacted toform a pressed article. Using a moving edge or brush powder is removedfrom the pressed article and is admixed with the breathing air of thepatient. The process is not suitable for mass production, because it isnot possible to produce with a homogeneous hardness the pressed articlesformed from tile medicinal substance and adjuvant.

DE-A-40 27 391 discloses a further propellant-free inhalator with asimilar construction. In order to make the breathed in substancequantity reproducible and simultaneously attain inhalable particles, anair volume stored in a cylinder is automatically released in reaction tothe breathing in and is led to a nozzle, so that the dosed substance isblown by the active air flow which forms into the throat of the patient.However, in connection with respiration triggering problems are causedby the considerable effort and expenditure necessary for a precise airvolume release triggered by respiration.

However, known processes and apparatuses generally suffer from thedisadvantage that there is an imprecise aerosol with respect to theparticle spectrum and mist density. Fundamentally, on blowing in, thereis a whirling up or turbulent agitation of a considerable air quantity,which is much larger than the blown in volume. This air quantity mustnormally be trapped in a corresponding container if not inhaled by thepatient. If it is directly inhaled by the patient, then theintrabronchial deposition differs to a very marked extent, because as afunction of the inhalation flow the particle spectrum is greatlymodified mainly by impaction.

On blowing in the accelerated air is decelerated by that which isalready present. Therefore the kinetic energy striking the aerosol isnot high.

If the blown in aerosol volume is intermediately stored in a container,so that the patient always inhales an identical particle spectrum, largevolumes are necessary. In the case of dosing aerosols it is oftennecessary to use as attached devices spacers having a volume of 300 to800 ml.

Another inhalator with an active air flow is known from WO-A-90/07351.The air flow is made ready by a pressurized gas source, or is producedwith the aid of a piston/cylinder arrangement, and is guided in a nozzlearrangement with a varying cross-section, in order to in planned mannerincrease the flow rate of the air flow. Close to the maximum flow ratein the nozzle arrangement a duct issues into the flow path andconstitutes a connection to a storage container for the pulverulentsubstance. The substance is sucked in by the active air flow andconveyed into a mixing chamber, where a good distribution of theparticles is to take place. In connection with this inhalator it must beborne in mind that the preparation of the aerosol takes place completelyindependently of the inhalation of the patient, and also an active airflow is directed into the respiratory tracts of the patient, so that agood distribution cannot be expected before and during inhalation.

SUMMARY OF THE INVENTION

The problem solved by the invention is to provide a process and anapparatus for producing an aerosol from a pulverulent substance withwhich a high density aerosol with inhalable, lung-reaching, and inparticular relatively small particles of the substance are madeavailable for inhalation, without having a disturbing influence on thebreathing in of the aerosol.

In the case of the invention, the whirling up or turbulent agitation ofthe pulverulent substance takes place in a clearly defined, closedwhirling or agitating chamber by the inflow of a gas, and in particularair. As a result of mechanically producing the vacuum by means of apiston or a pump a much lower pressure can be produced than would beachieved by the suction action of a patient. This permits a much higherinflow speed, which leads to the desired, good atomization of thesubstance particles. Subsequently the resulting aerosol, preferably alsoa clearly defined quantity or volume at normal pressure, is introducedinto the interior of a mouthpiece in a predetermined quantity,preferably in that there is initially a pressure increase in thewhirling or agitating chamber and then by opening an outlet thepredetermined aerosol quantity flows out up to pressure balance. Then,after closing the agitating chamber outlet, the patient or user canbreath in the aerosol from the mouthpiece.

The invention makes it possible to release and agglomerate a micronizedpowder in a small volume. The considerable air volume normally obtainedon blowing in the powder, and the resulting air excess, which is often amultiple of the blow-in air required, are rendered avoidable by thepresent invention. Therefore there is no longer any need forlarge-volume containers. The small volume is very precisely definableand leads to a dosage simplification. A stable aerosol forms, becauselarger particles are immediately separated by sedimentation. Unusuallyhigh powder densities of up to 10 mg/l can be achieved with the aid ofthe invention, and consequently correspondingly small dosing aerosolsare possible. In the process according to the invention the air flows ina clearly defined volume. Therefore the inflowing air always fills thesame volume. It leads to the deagglomeration and comminution of thepowder in an extremely high concentration. However, as statedhereinbefore, on blowing in a powder to bring it into an aerosol form,the turbulent agitation volume thins or rarefies the aerosol. In thecase of the process according to the invention there is such a highaerosol density that the limit concentration which can be carried by theair is reached. Thus, particularly the coarser particles are rapidlydeposited within seconds and this leads to a stable mist or aerosoldensity with a roughly identical particle spectrum. Such a high mistdensity cannot be achieved by blowing in. The mist density isindependent of the filling quantity as a result of the "supersaturation"of the air by the aerosol. This is not the case in known processes. Thisin itself sets aside the process and apparatus according to theinvention from the prior art. The small volume also has the importantadvantage of handiness.

According to preferred developments, prior to the inflow of a gas intothe whirling or turbulent agitation chamber, a pressure is producedtherein of below 100 Pa, such as approximately 70 Pa, preferably below50 Pa, e.g. 30 Pa and advantageously this is achieved in that theagitation chamber can be enlarged in the closed state for producing avacuum therein, and that after opening the outlet the gas flows into thesaid chamber as a result of the vacuum produced therein. This permitsflow rates in the agitating chamber of above 200 m/sec, which lead tothe desired deagglomeration by overcoming the adhesion of the particles.This produces a lung-reaching particle fraction of 90% and higher.

In the case of a vacuum the air flows in unhindered manner onto thepulverulent substance. The speed is only limited by the inertia of theair and the level of the vacuum. There is a very high mist densityproduction.

According to preferred developments the vacuum in the agitating chambercontaining the substance is produced by increasing the size of saidchamber and the aerosol is discharged from the chamber containing thesame by pressing out, and in particular the gas flowing into theagitating chamber is ambient air.

According to further preferred developments a mouthpiece connectable tothe agitating chamber can be sealed off with respect to the environmentduring the forcing of the aerosol into the mouthpiece and optionally upto an outlet of said mouthpiece for the subsequent breathing in by thepatient and/or a mouthpiece connectable with the agitating chamber,following the forcing in of the aerosol into the mouthpiece, is open tothe environment even when the user's mouth is attached thereto.

Whilst a turbulent air flow is produced for whirling purposes and isalso desired for this purpose, the air in and through the mouth of thepatient and his trachea and into the lung must flow in as laminar a wayas possible. According to a preferred development, the aerosol flows insubstantially laminar form into the mouthpiece, this being achieved inthat between the outlet of the agitating chamber and the interior of themouthpiece, a flow straightener is provided. The latter is in particularconstructed as a perforated plate.

According to further preferred developments of the invention, theagitating chamber is constructed in the storage chamber for thesubstance. In addition, between the inner area of a mouthpiece and theenvironment a closable opening is provided, when it opens the agitatingchamber outlet for the outflow of the aerosol from said chamber 18closed and/or between the interior of a mouthpiece and the environmentis provided a closable opening, which is opened on closing the agitatingchamber outlet. Whilst the opening to the interior of the mouthpiece onthe one hand and the agitating chamber outlet on the other can beindependently controlled in a suitable manner, according to a preferreddevelopment a closing member for the agitating chamber outlet and aclosing part for the opening between the interior of the mouthpiece andthe environment are interconnected, and in particular the closing memberand closing part are rigidly interconnected.

In order on the one hand to obtain an opening of the inlet and outletwith respect to the turbulent agitating chamber after producing a vacuumand without additional actuating processes, and on the other to obtainan outflow of the gas after opening the outlet with a predeterminedvolume by prior building up of an overpressure, according to furtherdevelopments the closing part for the agitating chamber outlet isconnected to a piston movable therein by means of a thread, and a pistonvarying the agitating chamber volume is connected to a tappet or pushrod for closing the outlet cooperating with a closing member of anoutlet of the agitating chamber.

In order that the movements of the piston in the cylinder are notimpeded by powder adhering to the inside of the cylinder wall, accordingto a preferred development the pulverulent substance and the agitatingchamber are surrounded by a flexible jacket positioned in the interiorof the cylinder, which is fixed on the one hand to the piston and on theother to the cylinder, close to its end remote from the piston, i.e.close to the inlet and outlet.

According to a further development, with the closing member associated astripping ring fixed to the cylinder.

As in the case of the apparatus according to the invention apredetermined substance is present, only a given number of aerosole canbe produced. In order to make it possible to detect the emptying of thecylinder, a counter or meter is provided. According to a preferreddevelopment, is formed by the fact that on an operating rod of thepiston in the cylinder is provided a flexible nose, which acts on asmall gear or a pinion, which by means of a worm constructed on one endface drives a larger gear, which is provided with colour markings, whichcan be observed through a window. In place of the gear it is alsopossible to provide a toothed belt provided with corresponding markings.

According to another preferred development, an opening leading into theturbulent agitating chamber is formed in the piston, the latter beingrigidly connected to an outer, cylindrical casing by means of a pistonrod end a web arranged transversely in the casing and the cylinder isformed by a cylindrical cylinder body with an internal diameter adaptedto the piston, and the cylinder is displaceable in the casing in such away that the agitating chamber can be enlarged. According to a furtherdevelopment, a closing part is provided, which is fitted to one arm of atwo-armed lever mounted on the piston rod, the cylinder body having anose which cooperates with another arm of the lever, so that on reachingthe position of the cylinder body in which the agitating chamber is atits largest, the opening in the piston is freed.

According to a further preferred development, the agitating chamber isformed by a bellows, which is closed by cover plates at its end faces,and in one cover plate is provided a first valve mechanism for the flowof gas which flows into the evacuated agitating chamber and which isreleased by a release mechanism when the agitating chamber is at itslargest through the expansion of the bellows, and in particular a secondvalve mechanism is provided through which the gas present in theagitating chamber on compressing the bellows can escape therefrom. Thereis optionally a third valve means which is also released by the releasemechanism if, as a result of the expansion of the bellows, the agitatingchamber is in its largest state, and through which the aerosol producedin said chamber can be discharged. It is also possible to provide abreathing tube, to which is connected the first and third valve meansand which has a constriction in the area between the two connectingpoints of the valve mechanisms through which the flow rate of the airflow on breathing through the breathing tube is increased.

The invention provides a process and an apparatus in which the aerosolhas a high, inhalable active substance proportion in the case of a gooddosing constancy. It has been found that the inhalable active substancepercentage is 90%, whereas it only 20% in the prior art. Thus, theefficiency is greatly increased by the invention, and much less activesubstance can be used because it is better utilized. The quantityvariation was much less than in the case of known processes andapparatuses, namely only 11%, whereas the variation coefficient in theknown processes and apparatuses is a multiple thereof Moreover, asstated, compared with the prior art there is a relatively narrowparticle size distribution of approximately 0.6 to just below 6 μm,whereas larger particles virtually do not occur in the aerosol.

The process according to the invention and embodiments of the apparatusaccording to the invention are described in greater detail hereinafterrelative to the attached drawings, wherein;

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A to 1D illustrate a first embodiment of the apparatus accordingto the invention and the individual steps of the process according tothe invention.

FIG. 2 illustrate a second embodiment of the apparatus according to theinvention.

FIGS. 3A and 3B illustrate a third embodiment of the apparatus accordingto the invention.

FIG. 4A is a longitudinal sectional view through another preferredembodiment of the apparatus according to the invention with the valveclosed.

FIG. 4B is a longitudinal sectional view through the apparatus of FIG.4A with the valve open.

FIG. 4C is a sectional view taken section through the counter along lineI--I in FIG. 4A.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The process according to the invention will firstly be explained bymeans of a first embodiment of the apparatus according to the inventionand relative to FIG, 1. These and further embodiments of the apparatuswill be described in greater detail hereinafter.

FIG. 1A illustrates the first stage of the process, according to which aclearly defined quantity of pulverulent substance 1 is brought into aclosed whirling or turbulent agitating chamber 2. In the firstembodiment the closed agitating chamber 2 is the interior of a cylinder2a of a piston-cylinder arrangement. The substance can be introducede.g. by an opening 3 provided in the cylinder, but also by a speciallyprovided opening or in some other way; for example the piston 2b can bedrawn out of the cylinder 2a, the substance introduced, and then thepiston reinserted in the cylinder.

FIG. 1B illustrates the second stage of the process according to theinvention, in which a clearly defined vacuum is produced in thesubstance-containing agitating chamber 2. In the case of apiston-cylinder arrangement, said vacuum is obtained in simple manner inthat the piston 2b is brought from the advanced position shown in FIG.1A to the retracted position shown in FIG. 1B. The opening 3 of thecylinder 2a is closed with u suitable closing member 4. On producing thevacuum in the interior of the substance-containing agitating chamber 2the pulverulent substance 1 remains substantially uninfluenced, as canbe gathered from FIGS. 1A and 1B by the substance 1 in the vicinity ofthe piston 2b.

The third stage of the process according to the invention illustrated inFIG. 1C. According to this, a gas, and preferably ambient air, isallowed to flow rapidly, but in controlled manner, into thesubstance-containing agitating chamber 2. Thus, an air flow is producedwhich flows in rapid, but controlled, manner into the agitating chamber.In the represented embodiment, this takes place by opening the closingmember 4 of the opening 3. The resulting air flow is indicated by thearrows in FIG. 1C. It whirls up the pulverulent substance and ensures agood distribution of the particles in the available agitating chamber 2so that the desired aerosol 5 is produced and almost completely fillsthe agitating chamber. The particle distribution is brought about undervery precisely definable conditions because as a result of the size anddesign of the available agitating chamber 2 and the opening 3 throughwhich the air flow passes into said chamber, as well as through theposition thereof, the flow behaviour and consequently the turbulentagitation of the pulverulent substance can be determined to asignificant extent.

Thus, it is e.g. possible to control in planned manner the agglomerationand sedimentation of larger particles which are less suitable or evenunsuitable for inhalation. This assists the formation of a homogeneousaerosol with a constant density.

In the fourth stage of the process according to the invention and asillustrated in FIG. 1D, the aerosol 5 that has been produced isdischarged from the agitating chamber 2 and is made available forinhalation by the patient. In the first embodiment the aerosol isdischarged by simply forcing it out, in that the piston 2b is returnedto its advanced position. However, discharge can also take place in thatduring breathing in the patient sucks the aerosol produced from theagitating chamber. However, in all cases aerosol discharge takes placein such a way that a disturbing influencing of the inhalation process onbreathing in is avoided, because no whirling up is produced in plannedform during this stage. The aerosol 5 with a good particle distributionis available prior to discharge in the agitating chamber 2, which ituniformly fills. Therefore the discharge can be completely based on theconditions to be taken into consideration with respect to theinhalation. In particular, it is possible to avoid a disturbinginfluence on the breathing in by an excessive or forced air flow.

In order to bring about an optimum adaptation of the openings, to theirparticular task, separate openings can be provided for the inflow of airinto the evacuated agitating chamber and for the forcing out of theaerosol, as well as for introducing the substance into said chamber.

The construction of the first embodiment of the apparatus according tothe invention is apparent from the above description of the inventiveprocess by means of said embodiment.

Thus, the first embodiment of the apparatus comprises an arrangementconstituted by a cylinder 2a and a piston 2b, which together define awhirling or turbulent agitating chamber 2. The piston 2b is movablyarranged in the cylinder 2a and can be moved backwards and forwardsbetween an advanced and a retracted position. The size of the agitatingchamber can consequently be determined by means of the piston position.The agitating chamber 2 has an opening 3 through which the dosedsubstance 1 is brought into said chamber 2, through which a gas,preferably ambient air, which turbulently agitates the substance flowsin, and through which the produced aerosol 5 produced is discharged. Inorder that the agitating chamber 2 is closed during the production ofthe defined vacuum, a closing member 4 is provided.

So as to prevent any impairing of the mobility of the piston 2b in thecylinder 2a, in the interior of the latter can be provided an additionalflexible container, such as a bellows or a thin-walled plastic hose forthe reception of the substance. On enlarging the agitating chamber, i.e.on moving the piston 2b to the retracted position, there is also anenlarging of the flexible chamber as a result of the externally appliedvacuum. Preferably the flexible container is also fixed to the piston,so that it moves with the latter.

FIG. 2 shows a second embodiment of the apparatus according to theinvention, where a bellows 10 is used as the component defining theagitating chamber. The bellows 10 is closed at its end faces by means ofcover plates 10a, 10b. In the cover plate 10a there are three valves 11,12 and 13, whereof the constructionally identical valves 11 and 12 areused for the inflow of air into the evacuated agitating chamber 2 andfor the discharge of the aerosol therefrom, whilst the valve 13 allowsan escape of air on compressing the bellows 10. After again enlargingthe bellows 10 in order to produce a vacuum in the substance-containingagitating chamber 2, a slide 16 is operated as the release mechanism forthe valves 11 and 12, and as a result said two valves are opened, beingrepresented in FIG. 2 as hose valves.

By means of the two valves 11 and 12 the bellows 10, and therefore theagitating chamber 2, is connected in shunt manner to a breathing tube 15through which the patient breaths in and which for this purpose isprovided at one end with a mouthpiece for the patient. At this end ofthe breathing tube 15 is provided further valve 16, which prevents ablowing into the breathing tube. The breathing tube 15 has aconstriction 15a, so that as a result of the pressure drop an adequateair flow flows through the agitating chamber 2. Devices preventing thesubstance 1, particularly a pulverulent substance, passing into thevalves and therefore impairing the operation of the valves or the oralingestion of the substance 1 by means of the breathing tube 15 are notshown.

A third embodiment of the apparatus according to the invention is shownin FIGS. 3A and 3B. The apparatus comprises an outer cylindrical casing20 and an inner cylindrical cylinder body 21, which is movable in thecasing between two positions as shown in FIGS. 3A and 3B. In theinterior of the casing one end of a piston rod 22 is rigidly connectedto the casing 20 by means of a web 23 running transversely through saidcasing. At its other end the piston rod carries a piston 24, which isadapted to the internal diameter of the cylinder body 21 and defineswith the latter the agitating chamber 2. If the cylinder 21 is moved,the piston 24 slides on the inner wall of the cylinder body. In the thusdefined agitating chamber 2 is provided an additional flexible plasticcontainer 25 connected in gas-tight manner to the piston 24.

In the construction shown in FIG. 3A the turbulent agitating or whirlingchamber 2 has the smallest volume. The pulverulent substance 1 islocated in the flexible plastic container 25. From this startingposition, the cylinder body 21 is moved into the position shown in FIG.3B. During the movement a plug or stopper 26 closes an opening 27 in thepiston, so that as a result of the volume increase in that agitatingchamber 2, a vacuum forms and expands the flexible plastic container 25.On reaching the position shown in FIG. 3B, a nose 28 fitted to the innerwall of the cylinder body engages with an arm of a two-arm lever 29 onwhose other arm is located the plus 26 closing the opening. Thus, theopening 27 in the piston is freed, so that air flows into the evacuatedagitating chamber, the substance is agitated, and the aerosol produced.

The inner cylinder 21 is then drawn upwards again, and the aerosol isforced out of the agitating chamber through the opening 27 into theinterior of the cylinder. On the outer casing is fitted a mouthpiece 30through which the patient can suck the aerosol produced from the spacewithin the cylinder 21. For this purpose the cylinder 21 is hollow andis provided at a suitable point with a passage opening for the sucked-inaerosol. The cylinder body also has an air inlet 31 through which theambient air on inhaling passes into the interior of the cylinder body.The air flow in through the air inlet moves the aerosol with thewhirled-up substance out of the cylinder body, so that the substance iscompletely inhaled.

The plug-carrying two-arm lever 29 is either pretensioned in such a waythat the plus 26 closes the opening 27 in the piston in its inoperativeposition and only as a result of the action of the nose 28 in theinterior of the cylinder body 21 or as a result of the internal pressureof the agitating chamber 2 on moving back the cylinder body 21 into itsstarting position frees the opening 27, or it is brought with the aid ofa thread 32 into the closing position just before the starting positionis reached. FIGS. 4A to 4C show an extremely preferred development of anapparatus according to the invention for producing an aerosol and forperforming the process according to the invention. The same parts aregiven the same reference numerals as in the preceding drawings.

In a cylinder 2a the apparatus has a whirling or turbulent agitatingchamber 2, in which is also housed all the substance to be agitated. Thevolume change of the agitating chamber 2 is brought about by a piston2b, which is displaceable in the cylinder 2a. On the side of theagitating chamber opposite to the piston 2b is provided a closing member4 in the form of a valve. The piston 2b is displaceable by means of apiston rod 34 projecting from the cylinder 2a , using a grip or handle34a connected thereto.

The piston is provided with packings 35. With its end face 36 extendingto the agitating chamber 2, a flexible sleeve 37 in the form of a latexdiaphragm or the like is connected, in much the same way as in theconstruction of FIGS. 3A and 3B, and is fixed to the wall of thecylinder 2a at 38 in the vicinity of the closing member 4. The agitatingchamber 2 is constructed within the sleeve 37, the substance 1 alsobeing located in said sleeve. This ensures that the material does notstick to the inner wall of the cylinder 2a and impede the movement ofthe piston 2b.

A push rod 39, whose function will be explained hereinafter, projectsfrom the end face 36 of the piston 2b, facing the agitating chamber 2and into the latter. The closing member 4 has a movable valve body 41and a valve seat 42. The valve seat 42 formed by a sealing ring 43,which tightly engages on the valve body 41 in the closed state. On theside remote from the agitating chamber 2, the valve body 41 is providedwith a conical face 45 which slides along the sealing ring 43 on againmoving the valve of the closing member 4. The inside of the sealing ringis preferably cutting edge-like or rounded, and not cylindrical.

Spaced from the scaling ring 43 in the direction of the agitatingchamber 2, an elastic stripping ring 46 is fixed to the cylinder 2a andcooperates with a flat cylinder 47 which has a larger diameter than thevalve body and which is connected to the latter with respect to thechamber 2. The valve body 41 and cylinder body 47 can be constructed inone piece.

In the cylinder body 47 is formed a centrosymmetrical, frustum-shapedrecess 48, which cooperates with a frustum-shaped, front end 49 of thepush rod 39 in a manner to be described hereinafter.

To the cylinder 2a is connected a mouthpiece 51, whose main extensiondirection is at right angles to that of the cylinder 2a. The mouthpiecehas an outlet channel 53 leading to an outlet 52.

A perforated plate 55 is positioned between the outlet area 54 of theagitating chamber 2 behind the closing member 4 end the outlet channel53 through which the aerosol forced out of the chamber 2, can be forcedout of the opening 52, the aerosol flow being straightened, i.e. broughtinto a substantially laminar flow and aerosol turbulence caused by thewhirling up in the agitating chamber 2 is substantially suppressed.

In a partition 56 of the mouthpiece 51, remote from the closing member 4and preferably aligned with the latter, is formed an opening 57 whichcan be closed by a closing plate 58 which is closable by means of anaxial attachment 59 of the valve body 41 on opening the latter and isopened when the valve body 41 is closed.

The opening 57 issues into an intermediate space 60, which is connectedwith the environment by openings 60b in the cylinder wall 2a on itsinside coverable by flaps 60 a acting as check valves. Thus, by means ofthe openings 60b and the openings 57, air can be sucked In, but notforced out.

As stated, at the end of the cylinder 2a remote from the mouthpiece 51is provided a counter 33. For this purpose on the piston rod 34 isformed a resilient nose 61 which acts on a pinion 62 whose axis isoriented perpendicular to the axis of the piston rod 34. On the remoteend face of the pinion 62 is constructed a worm 62a which engages in alarge gear rim 63 with internal teeth. The axis of gear rim 63 parallelto the axis of the piston rod 34, and optionally coincides therewith. Onthe outside of the gear rim 63 are provided markings which can be seenthrough a window.

Alternatively it would be possible to provide a toothed belt, operablein the same way by means of a resilient attachment on the piston rod 34and having colour markings visible through a window. Thus, it ispossible in both cases to establish whether the intended number ofoperations has been performed and therefore whether the substanceoriginally introduced into the apparatus has been used up.

The apparatus according to this development of the invention functionsas follows. The piston 2b is advanced from the position shown in FIG.4A, where at its highest it projects so far upwards, i.e. towards themouthpiece 51, that the tip 49 of the attachment 39 projects into theconical recess 48 of the plate 47 and is drawn downwards by means of thehandle 33, i.e. from the mouthpiece 51. The closing member 4 is closed.As a result the agitating chamber 2 is provided with a vacuum.

Shortly before the piston 2b reaches the end face of the cylinder 2aremote from the mouthpieces 51, the tension-proof thread 40, which isalso relatively inelastic with respect to tension and which is fixedbetween the valve body 41 and the extension or attachment 39 of thepiston 2b, is in its tensioned position. A further drawing down of thepiston 2b to the end face remote from the mouthpiece 51 ensures that theclosing member 4 is opened by the drawing down of the valve body 41(FIG. 4B). Simultaneously the opening 47 is closed by the closing plate58.

Through the opened closing member 4, by means of the opening 52 of themouthpiece, air can flow into the agitating chamber 2 as a result of itsvacuum, so that the substance 1 therein is whirled up, and consequentlyan aerosol is formed.

Subsequently, by means of the handle 33, the piston 2b is again forcedonto the mouthpiece 51. The aerosol formed in the agitating chamber 2 isinitially forced out of the same and pressed through the perforatedplate 55 into the channel 53 of the mouthpiece 51 until the front tip 49of the piston extension 39 engages in the recess 48 of the plate 47 ofthe closing member 4 and again closes the latter. Simultaneously theopening 57 is opened, in that the closing plate 58 is raised from it.

For so long as the opening 57 is closed and therefore the closing member4 opened, the user is unable to breath in from the apparatus accordingto the invention. This prevents an undefined aerosol quantity beingsucked by breathing in from the agitating chamber 2. Thus, during theforcing out of aerosol from the agitating chamber 2 and the opening timeof the closing member 4, the opening 57 is closed, so that a preciselydefined aerosol quantity is brought from the chamber 2 into themouthpiece 51 as is determined by the stroke of the piston 2b. If duringthis time the opening 57 were opened, then counterflow air could flow inthrough the opening 57 and the opened closing member 4 into theagitating chamber 2, so that as a result of breathing in the user couldsuck in a non-defined aerosol quantity from the agitating chamber 2.

After opening the opening 57, the user can inhale the aerosol in thechannel 53 of the mouthpiece 51. Air can subsequently flow via theopening 60b, the space 60 and the opening 57, because during suction theflaps 60a are raised from the opening 60b to free the latter (FIG. 4A).Subsequently the apparatus according to the invention is ready forreuse.

What is claimed is:
 1. A process for producing an aerosol, comprisingthe steps of:(a) inserting a precisely defined quantity of a pulverulentsubstance into a chamber having a predetermined volume; (b) evacuatingthe chamber with the pulverulent substance therein to produce at least apartial vacuum in the chamber; (c) allowing a gas to flow into theevacuated chamber to cause the pulverulent substance therein to whirl upand form an aerosol; and (d) immediately after step (c), forcing apredetermined volume of the aerosol from the chamber.
 2. A processaccording to claim 1, wherein step (b) comprises reducing the pressurewithin the chamber to a pressure of not more than 100 Pa.
 3. A processaccording to claim 1, wherein step (b) comprises increasing the size ofthe chamber.
 4. A process according to claim 1, wherein step (b)comprises reducing the pressure within the chamber by means of suction.5. A process according to claim 4, wherein step (b) comprises activatinga motor-driven pump to reduce the pressure within the chamber.
 6. Aprocess according to one of the claims 1 and 2 to 4, wherein step (d)comprises forcing the aerosol out of the chamber.
 7. A process accordingto claim 1, wherein the chamber includes a mouthpiece, and step (d)comprises sealing off the mouthpiece with respect to the environment,and forcing the aerosol into the mouthpiece.
 8. A process according toclaim 1, wherein the chamber includes a mouthpiece, and step (d)comprises forcing the aerosol into the mouthpiece, and then opening themouthpiece to the environment.
 9. A process according to claim 1,wherein step (d) comprises causing the aerosol to flow in asubstantially laminar manner.
 10. A process according to claim 1,wherein step (b) comprises reducing the pressure within the chamber to apressure of not more than 50 Pa.
 11. An apparatus for producing anaerosol from a pulverulent substance, said apparatus comprising:astorage chamber having a predetermined volume, with at least one openingthereinto, and having therein a precisely defined quantity of thepulverulent substance; first openable closing means for closing the atleast one opening of the storage chamber; means for producing a vacuumin the storage chamber, thereby generating an evacuated storage chamber;means for introducing a gas through the at least one opening into theevacuated storage chamber to cause the pulverulent substance therein towhirl up and form an aerosol; and means for forcing a predeterminedvolume of the aerosol through the at least one opening from the storagechamber.
 12. An apparatus according to claim 11, wherein the means forproducing the vacuum comprises a pump connected to the at least oneopening.
 13. An apparatus according to claim 11, wherein the means forproducing a vacuum comprises means for enlarging the volume of thechamber while the closing means is closing the at least one opening. 14.An apparatus according to claim 13, wherein the means for introducing agas comprises means responsive to opening of the first closing means topermit the gas to flow into the storage chamber as a result of thevacuum therein.
 15. An apparatus according to one of the claims 13 and14, wherein the storage chamber comprises a cylinder, and the vacuumproducing means comprises a piston within the cylinder permittingenlargement of the storage chamber by the displacement of the pistonwith respect to the cylinder.
 16. An apparatus according to claim 15,wherein:the at least one opening of the storage chamber passes throughthe cylinder, and the first closing means comprises a closure member forclosing the at least one opening of the storage chamber, and a threadconnecting said closure member to said piston to pull said closuremember from the at least one opening as said piston moves, opening theat least one opening.
 17. An apparatus according to claim 15,wherein:the at least one opening of said storage chamber passes throughsaid cylinder, and said first closing means comprises a closure memberfor closing the at least one opening of said storage chamber, and a pushrod connecting said closure member to said piston to push said closuremember from the at least one opening as said piston moves, opening theat least one opening.
 18. An apparatus according to one of the claim 11,wherein:the storage chamber includes an agitating chamber having anoutlet, second openable closing means for closing the agitating chamberoutlet, a mouthpiece having a first end communicating with the agitatingchamber outlet and a second end, a first opening communicating with themouthpiece first end and the agitating chamber outlet, and a secondopening communicating with the mouthpiece second end for removal of theprecisely defined volume of the aerosol therethrough; and the firstclosing means includes means responsive to opening of the agitatingchamber outlet for closing the storage chamber first opening.
 19. Anapparatus according to claim 18, wherein said responsive means isfurther responsive to closing of the agitating chamber outlet, foropening the storage chamber first opening.
 20. An apparatus according toclaim 19, wherein said responsive means includes connecting meansinterconnecting the first closing means and the second closing means.21. An apparatus according to claim 20, wherein said connecting means isa rigid connecting means.
 22. An apparatus according to claim 11,further comprising a flow straightener connected to the storage chamberoutlet, and a mouthpiece connected to the flow straightener for removaltherethrough of the aerosol in a laminar flow.